Oncogerminative hypothesis of tumor formation

Vinnitsky, V. B.

doi:10.1016/0306-9877(93)90191-r

Cited by 20 publications

(27 citation statements)

References 9 publications

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“…Particularly attractive, if theoretical, is the relationship he established between embryonic development and the functionality/heterogeneity (oncogerminative, oncotrophoblastic, and oncosomatic entities) of cancer cells. Some of our findings, in particular those related to pregnant and monastery cells, are consistent with his theory (Vinnitsky, 1993). Rajaraman has introduced the neosis theory that tries to explain the replication mechanism of multinucleated cells.…”

Section: Hirtenzellen or Shepherd Cellssupporting

confidence: 76%

“…Certain events observed during the evolution of cell heterogeneity from multinucleated polyploid cells appear to be linked to the oncogerminative theory of tumor formation suggested by Vinnitsky, who elegantly proposed that the malignant transformation of somatic cells is based on the activation of embryogenic programs that confer phenotypical features of germ cells, the ability to multiply via parthenogenesis, and the formation of oncospheroids containing three different cell types: oncogerminative (stem), oncotrophoblastic, and oncosomatic entities. Oncospheroids pass through two phases: vascularization (in vivo) and the development of metastatic secondary cells (Vinnitsky, 1993). This process can be regarded as an analogy to the embryonic migration and further differentiation of germ cells in a strictly coordinated balance of senescence/apoptosis and cell survival.…”

Section: Introductionmentioning

confidence: 99%

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Atypical Cell Populations Associated with Acquired Resistance to Cytostatics and Cancer Stem Cell Features: The Role of Mitochondria in Nuclear Encapsulation

Díaz-Carballo

Gustmann

Jastrow

et al. 2014

DNA and Cell Biology

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Until recently, acquired resistance to cytostatics had mostly been attributed to biochemical mechanisms such as decreased intake and/or increased efflux of therapeutics, enhanced DNA repair, and altered activity or deregulation of target proteins. Although these mechanisms have been widely investigated, little is known about membrane barriers responsible for the chemical imperviousness of cell compartments and cellular segregation in cytostatic-treated tumors. In highly heterogeneous cross-resistant and radiorefractory cell populations selected by exposure to anticancer agents, we found a number of atypical recurrent cell types in (1) tumor cell cultures of different embryonic origins, (2) mouse xenografts, and (3) paraffin sections from patient tumors. Alongside morphologic peculiarities, these populations presented cancer stem cell markers, aberrant signaling pathways, and a set of deregulated miRNAs known to confer both stem-cell phenotypes and highly aggressive tumor behavior. The first type, named spiral cells, is marked by a spiral arrangement of nuclei. The second type, monastery cells, is characterized by prominent walls inside which daughter cells can be seen maturing amid a rich mitochondrial environment. The third type, called pregnant cells, is a giant cell with a syncytium-like morphology, a main nucleus, and many endoreplicative functional progeny cells. A rare fourth cell type identified in leukemia was christened shepherd cells, as it was always associated with clusters of smaller cells. Furthermore, a portion of resistant tumor cells displayed nuclear encapsulation via mitochondrial aggregation in the nuclear perimeter in response to cytostatic insults, probably conferring imperviousness to drugs and long periods of dormancy until nuclear eclosion takes place. This phenomenon was correlated with an increase in both intracellular and intercellular mitochondrial traffic as well as with the uptake of free extracellular mitochondria. All these cellular disorders could, in fact, be found in untreated tumor cells but were more pronounced in resistant entities, suggesting a natural mechanism of cell survival triggered by chemical injury, or a primitive strategy to ensure stemming, self-renewal, and differentiation under adverse conditions, a fact that may play a significant role in chemotherapy outcomes.

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Section: Hirtenzellen or Shepherd Cellssupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Atypical Cell Populations Associated with Acquired Resistance to Cytostatics and Cancer Stem Cell Features: The Role of Mitochondria in Nuclear Encapsulation

Díaz-Carballo

Gustmann

Jastrow

et al. 2014

DNA and Cell Biology

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“…The parthenogenetic theory of cancer was first suggested by Beutner [60] (cited from Erenpreiss [2]) and updated more recently by Vladimir Vinnitsky [3, 61]. This link is also made more apparent with a series of recent studies reporting the spherogenicity and malignancy of endopolyploid tumour cells (ETC).…”

mentioning

confidence: 99%

The “virgin birth”, polyploidy, and the origin of cancer

et al. 2014

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Recently, it has become clear that the complexity of cancer biology cannot fully be explained by somatic mutation and clonal selection. Meanwhile, data have accumulated on how cancer stem cells or stemloids bestow immortality on tumour cells and how reversible polyploidy is involved. Most recently, single polyploid tumour cells were shown capable of forming spheroids, releasing EMT-like descendents and inducing tumours in vivo. These data refocus attention on the centuries-old embryological theory of cancer. This review attempts to reconcile seemingly conflicting data by viewing cancer as a pre-programmed phylogenetic life-cycle-like process. This cycle is apparently initiated by a meiosis-like process and driven as an alternative to accelerated senescence at the DNA damage checkpoint, followed by an asexual syngamy event and endopolyploid-type embryonal cleavage to provide germ-cell-like (EMT) cells. This cycle is augmented by genotoxic treatments, explaining why chemotherapy is rarely curative and drives resistance. The logical outcome of this viewpoint is that alternative treatments may be more efficacious - either those that suppress the endopolyploidy-associated ‘life cycle’ or, those that cause reversion of embryonal malignant cells into benign counterparts. Targets for these opposing strategies are components of the same molecular pathways and interact with regulators of accelerated senescence.

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“…These results are in line with the hypothesis of tumors 206 are described as aberrations of growth, differentiation, and organization of cell 207 populations. These are basic processes that are tightly coordinated and controlled 208 during embryogenesis as well as in adult tissues [6]. The oncogerminative theory of cancer development (OTCD) [6] suggests that cancer arises due to aberrant expression 210 of developmental genes.…”

mentioning

confidence: 99%

“…These are basic processes that are tightly coordinated and controlled 208 during embryogenesis as well as in adult tissues [6]. The oncogerminative theory of cancer development (OTCD) [6] suggests that cancer arises due to aberrant expression 210 of developmental genes. According to this theory, tumor formation is a dynamic 211 self-organizing process that mimics the process of early embryo development.…”

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confidence: 99%

Master regulators of signaling pathways coordinate key processes of embryonic development in breast cancer

Tapia-Carrillo

Tovar

et al. 2018

Preprint

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Signal transduction pathways allow cells to respond to environmental cues and can induce intracellular changes. In some contexts, like embryonic development, signal transduction plays crucial roles in cell fate determination and differentiation, while in developed organisms some of this processes contribute in the maintenance of the structural integrity of tissues.Tumor cells are recognized as having deregulated signaling which leads to a series of abnormal behaviors known as the hallmarks of cancer. Although gene regulation is often viewed as the last step in signal transduction, transcriptional regulation of the components of a pathway may impact in the long term deregulation observed in tumors. The study of gene regulatory networks centered around genes of the signal transduction pathways allows the identification of transcriptional regulators with the greatest influence over the signal transduction gene signature, also denominated Master Regulators.In this work we identify, the master regulators that regulate the expression of genes of 25 relevant pathways grouped in KEGG within the category of signal transduction in a breast cancer dataset. For this purpose we implemented a modified MARINa algorithm that identifies, from a network of regulons, those that possess more differentially expressed genes related to the process to be studied. We identified CLOCK, TSHZ2, HOXA2, MEIS2, HOXA3, HAND2, HOXA5, TBX18, PEG3 and GLI2 as the top 10 master regulators of signaling pathways in breast cancer. Nine of them are recognized for taking part in embryonic development associated processes.Individual enrichment GO biological function for each TMR regulons showed to be significantly enriched in embryonic development related processes. Hedgehog signaling pathway was shown as enriched and also highly deregulated. The genes of the HOXA family are shared among most of the TMRs. Overall, this suggests the importance of the aberrant reprogramming of mechanisms present during embryonic development, being coopted in favor of tumor development.

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Oncogerminative hypothesis of tumor formation

Cited by 20 publications

References 9 publications

Atypical Cell Populations Associated with Acquired Resistance to Cytostatics and Cancer Stem Cell Features: The Role of Mitochondria in Nuclear Encapsulation

Atypical Cell Populations Associated with Acquired Resistance to Cytostatics and Cancer Stem Cell Features: The Role of Mitochondria in Nuclear Encapsulation

The “virgin birth”, polyploidy, and the origin of cancer

Master regulators of signaling pathways coordinate key processes of embryonic development in breast cancer

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